The first purpose of these investigations is to define some of the cellular and molecular aspects of T- and B-cell differentiation through comparative studies in mice, rabbits, chickens, frogs and humans. Integrated studies of individuals with leukemias, lymphomas and immunodeficiences will be the other major focus. We will examine the nature of the immunoglobulin components expressed by pre-B cells from normal tissues, cell lines and pre-B hybridomas, with emphasis on the genetic diversity of variable regions of IgM heavy chains. Anti-idiotype antibodies will be used to examine normal generation of clonal diversity, the cellular basis of pauciclonal antibody responses and the extent of clonal involvement of murine plasmacytomas and a spectrum of B-cell malignancies in humans. Generation of isotype diversity will be re-examined in chickens and man. The immunosuppressive effects of anti-Ia will be investigated along with phylogenetic aspects of Ia structure and function. We will continue to examine human T-cell subpopulations, and search for V H expression by human T cells. Hybridoma antibodies will play a central role in these studies, and somatic cell hybridization used to examine generation of V H and isotype diversity and to map genes for human immunoglobulins.